Histone methylation is required for oogenesis in Drosophila
Histone methylation is required for oogenesis in Drosophila
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DOI：
10.1242/dev.02698
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发表时间：
2007-01-01
期刊：
影响因子：
4.6
通讯作者：
Hazelrigg, Tulle
中科院分区：
文献类型：
--
作者：
Clough, Emily;Moon, Woongjoon;Hazelrigg, Tulle
SET结构域蛋白是组蛋白赖氨酸甲基转移酶(HMTs)，在发育过程中发挥重要作用。在这里，我们首次证明了组蛋白甲基化发生在果蝇卵巢的生殖细胞和体细胞中，并在体内证明了卵子发生所必需的HMT，这是无蛋(卵)基因的产物。鸡蛋是一种SET结构域蛋白，类似于人类蛋白SETDB1及其小鼠同源基因ESET。这些蛋白质是包含分叉集结构域的HMT小家族的成员。由于组织培养细胞中SETDB1的缺失是细胞致死的，并且ESET突变会导致早期胚胎停滞，SETDB1/ESET在发育中的作用已被证明是很难解决的。我们发现，在果蝇卵巢中，组蛋白H3的K9残基的三甲基化需要卵子。在携带删除设定区域的卵子等位基因的雌性中，卵子发生在早期就停止了。这种停滞伴随着卵室形成所需的体细胞增殖减少，以及生殖细胞和体细胞群体的凋亡。我们认为，其他密切相关的SET结构域蛋白在其他物种的配子发生中可能具有类似的功能。
SET domain proteins are histone lysine methyltransferases (HMTs) that play essential roles in development. Here we show for the first time that histone methylation occurs in both the germ cells and somatic cells of the Drosophila ovary, and demonstrate in vivo that an HMT, the product of the eggless (egg) gene, is required for oogenesis. Egg is a SET domain protein that is similar to the human protein SETDB1 and its mouse ortholog ESET. These proteins are members of a small family of HMTs that contain bifurcated SET domains. Because depletion of SETDB1 in tissue culture cells is cell-lethal, and an ESET mutation causes very early peri-implantation embryonic arrest, the role of SETDB1/ESET in development has proven difficult to address. We show that egg is required in the Drosophila ovary for trimethylation of histone H3 at its K9 residue. In females bearing an egg allele that deletes the SET domain, oogenesis arrests at early stages. This arrest is accompanied by reduced proliferation of somatic cells required for egg chamber formation, and by apoptosis in both germ and somatic cell populations. We propose that other closely related SET domain proteins may function similarly in gametogenesis in other species.